Method for preparing derivatives of fungicidal iodochromones

ABSTRACT

This invention relates to new methods for preparing chemical compounds, in particular fungicidal compounds, especially iodinated derivatives of chromones, preferably compounds of formula (I), and intermediate compounds useful for these methods.

This invention relates to new methods for preparing chemical compounds,in particular fungicidal compounds, especially iodinated derivatives ofchromones, preferably compounds of formula (I), and intermediatecompounds useful for these methods.

The subject of the present invention is also a method for preparingvinylalkoxides from vinylamines; it relates more particularly to thepreparation of 2-halo and 2-alkoxychromones by the reaction of a2-aminochromone with a copper halide or alkoxide.

The subject of the present invention is also a method for preparing2-aminochromones by reacting an alkyl salicylate with an alkylnitrileand a base, followed by cyclization in an aqueous acid medium.

European patent application EP-861 242, which relates to fungicidalcompounds derived from coumarin or chromone, generically reviews methodsfor preparing some of these compounds. However, even though two examplesof iodinated compounds are disclosed, no specific method for preparingsuch iodinated derivatives is mentioned, nor is such an improved methodsuggested.

There are known from the prior art various methods allowing thepreparation of aromatic halides from primary aromatic amines via aSandmeyer reaction. There is known in particular the preparation ofaromatic diazonium salts (March's Advanced Organic Chemistry, 5^(th)edition, John Wiley & Sons, Inc., (2001), p816-817 and 936) and thechemical reactions associated with such diazonium salts (Chem. Rev.,(1988), 88, 765-792). However, none of the known methods describes suchconversions to a vinyl ether series according to the scheme below inwhich * represents a free site, G¹ represents a halogen atom or analkoxide and for which the structures are linear or cyclic which may bearomatic or otherwise:

During the preparation of the fungal compounds covered by the presentinvention, the following problems are often encountered:

-   -   difficulty of improving the methods both from a technical point        of view and from an economic point of view;    -   low yield;    -   insufficient purity;    -   difficulty of recycling the reagents used;    -   low rate of conversion;    -   reduction in the number of steps;    -   use of more economical agents;    -   improvement in the simplicity and safety of the reactions used;    -   limiting the number of by-products formed;    -   limiting side reactions.

The present invention makes it possible to solve all or some of theseproblems or disadvantages. It makes it possible in particular to avoidor to limit the substitution of halogen atoms by an alcoholate groupwhen it is present, in particular when the structure comprises twohalogen atoms.

A first aspect of the invention relates to the preparation of a compoundof formula (I)

according to the following steps:step A:reaction of a compound of formula (V)

with a nitrile of formula R¹CH₂CN and a base to form the compound offormula (1);

step B:compound of formula (IV) which is then cyclized in an aqueous acidmedium to form the compound of formula (III):

step C:compound of formula (III) which gives the compound of formula (II) via adiazotization reaction by means of a compound chosen from sodium nitritein the form of a mixture with an acid, alkyl nitrites, alkylthionitrites and alkyl thionitrates, and decomposition by means of acompound AZ_(n);

step D:compound of formula (II) which gives the compound of formula (I) by theaction of an alcohol in the form of a mixture with a base;in the formulae (I) to (V)

-   -   R¹, R², R³ and R⁴, which are identical or different, represent a        C₁-C₁₀ alkyl, C₁-C₁₀ alkenyl or C₁-C₁₀ alkynyl, one or more        carbo- or heterocycles having 5 to 7 atoms, it being possible        for these groups to be substituted or unsubstituted;    -   A represents a metal or a metal salt;    -   Z represents a group chosen from Cl, Br or —OR³;    -   n is equal to 0, 1 or 2.        For R¹, noncyclic substituents or optionally aromatic cyclic        substituents are preferred, and for Z, Cl is preferred.

When the groups or radicals of the compounds of formula (I) to (V) aresubstituted, they are preferably substituted with one or more groupswhich may be chosen, independently of each other, from an alkyl radical,alkenyl radical, alkynyl radical, a halogen atom, a cyano radical,trialkylsilyl radical, alkoxy radical, alkylthio radical, hydroxylradical, nitro radical, amino radical, acyl radical, acyloxy radical,phenyl radical, heterocyclyl radical, phenylthio radical, phenoxyradical, heterocyclyloxy radical, heterocyclylthio radical and oxidizedand optionally substituted derivatives of chemical entities containing athio group.

The term heterocyclyl comprises heteroaryl groups and nonaromaticheterocyclyl groups, which may be saturated or unsaturated. Theheteroaryl groups are generally 5- or 6-membered rings containing up to4 heteroatoms chosen from nitrogen, oxygen and sulfur, optionally fusedwith a benzene ring. As examples of heteroaryl groups, there may bementioned groups derived from thiophene, furan, pyrrole, thiazole,oxazole, imidazole, isothiazole, oxazole, pyrazole, 1,3,4-oxadiazole,1,3,4-thiadiazole, 1,2,4-oxadiazole, 1,2,4-thiadiazole, 1,2,4-triazole,1,2,3-triazole, tetrazole, benzo[b]thiophene, benzo[b]furan, indole,benzo[c]thiophene, benzo[c]furan, isoindole, benzoxazole, benzothiazole,benzimidazole, benzisoxazole, benzisothiazole, indazole,benzothiadiazole, benzotriazole, dibenzofuran, dibenzothiophene,carbazole, pyridine, pyrazine, pyrimidine, pyridazine, 1,3,5-triazine,1,2,4-triazine, 1,2,4,5-tetrazine, quinoline, isoquinoline, quinoxaline,quinazoline, cinnoline, 1,8-naphthyridine, 1,5-naphthyridine,1,6-naphthyridine, 1,7-naphthyridine, phthalazine, pyridopyrimidine,purine or pteridine.

The nonaromatic heterocyclyl groups are generally 3-, 5-, 6- or7-membered rings containing up to 3 heteroatoms chosen from nitrogen,oxygen and sulfur, for example oxiranyl, thiiranyl, thiazolinyl,dioxolanyl, 1,3-benzoxazinyl, 1,3-benzothiazinyl, morpholino,pyrazolinyl, sulfolanyl, dihydroquinazolinyl, piperidinyl, phthalimido,tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, indolinyl,2-oxopyrrolidino, 2-oxobenzoxazolin-3-yl or tetrahydroazepinyl.

The substituents, when they are present, on the phenyl or heterocyclylgroups may be for example halogen atoms, CN, NO₂, SF₅, B(OH)₂,trialkylsilyl, acyl, O-acyl or a radical E, OE or S(O)_(n)E as definedabove for R¹ or alternatively an optionally substituted amino radical;or alternatively two adjacent groups on the ring, together with theatoms to which they are attached form a carbocyclic or heterocyclicring, which may be optionally substituted in a similar manner.

The term acyl comprises acid residues containing sulfur or phosphorusand carboxylic acid residues. Examples of acyl groups are thus —COR⁵,—COOR⁵, —CONR⁵R⁶, —CON(R⁵)OR⁶, —COONR⁵R⁶, —CON(R⁵)NR⁶R⁷, —COSR⁵, —CSSR⁵,—S(O)_(q)R⁵, —S(O)₂OR⁶, —S(O)_(q)NR⁵R⁶, —P(=L)(OR⁵)(OR⁶) or —COOR⁵, inwhich R⁵, R⁶ and R⁷, which may be identical or different, represent ahydrogen atom, an optionally substituted alkyl radical, optionallysubstituted cycloalkyl radical, optionally substituted cycloalkenylradical, optionally substituted alkenyl radical, optionally substitutedalkynyl radical, optionally substituted phenyl group or optionallysubstituted heterocyclyl group, or alternatively R⁵ and R⁶, or R⁶ andR⁷, together with the atom(s) to which they are attached, may form aring, q represents 1 or 2 and L represents O or S.

Where appropriate, the amino radicals may be substituted for examplewith one or two optionally substituted alkyl or optionally substitutedacyl radicals, or alternatively two substituents may form a ring,preferably a 5- to 7-membered ring, which may be substituted and whichmay contain other heteroatoms, such as for example morpholine.

Where appropriate, persons skilled in the art will know how to adapt thereaction conditions according to the groups present, in particular bysuitably protecting them.

The combination of steps A and B, as well as the combination of steps Cand D, taken separately constitute methods which also form part of thepresent invention as such. The reagents, the reaction conditions and theoptional variant steps are similar to those described for the method ofthe invention comprising steps A to D.

The compounds of formula (V) may be prepared in a manner similar to whathas been reported in the literature for alkyl 3-halosalicylates fromequivalent alkyl salicylates, see for example Pharm. J., (1947), 159,182.

During the condensation reaction of step A using the compound of formula(V) to give the compound of formula (IV), a homogeneous or heterogeneousinorganic or organic base, preferably a lithium alkylamide, for examplelithium diisopropylamide, is advantageously used.

Advantageously, the base useful for this step may consist of a mixtureof such bases. Persons skilled in the art will know how to determine thenumber and the relative quantities of these bases used as a mixture.

The compound of formula (IV) can be characterized but is generally notisolated.

According to a variant A′ of this step A, the nitrile of formula R¹CH₂CNmay be replaced by a nitrile of formula R¹CXHCN in which X represents ahalogen atom and the base is then replaced by a metal, in particularmagnesium or zinc, see in particular Synth. Commun. (1989), 19(9-10),1649-53.

During step B, the compound of formula (IV) gives the compound offormula (III). An inorganic or organic acid is used; ammonium chloride,hydrochloric acid or acetic acid are suitable. Aqueous acetic acid ispreferred.

During step C, the compound of formula (III) gives the compound offormula (II) via a diazotization reaction, see for example March'sAdvanced Organic Chemistry, 5^(th) edition, John Wiley & Sons, Inc.(2001), p. 816, followed by a decomposition reaction.

As preferred reagents used for this diazotization reaction, sodiumnitrite, and alkyl nitrites, in particular t-butyl or methyl nitrites,may be mentioned. During the use of NaNO₂, the preferred acids are HCl,HBr, H₂SO₄.

Preferably, the diazo intermediate may be decomposed by means of acompound AZ_(n) chosen from a metal halide or alkoxide, preferably CuCl,CuBr, CuCl₂, CuBr₂, CuOR³ or Cu(OR³)₂; CuCl₂ and CuBr₂ may also be usedin their hydrated form.

The following combinations are particularly advantageous:

-   -   t-butyl or methyl nitrites and Cu(OR³)₂ or CUCl₂;    -   sodium nitrite with HCl or H₂SO₄ and CuOR³ or CuCl.

During this step C A therefore preferably represents copper. Othermetals useful for this step are mentioned in Chem. Rev., (1988), 88,765-792. This step C may also be carried out using NaNO₂ with ClSiMe₃ inorder to prepare a compound in which Z represents Cl; persons skilled inthe art will know how to adapt the conditions for such a Sandmeyerreaction known per se (Tet. Letters, 33 (22), 3167-3168 (1992)).

Likewise, NaNO₂, as a mixture with copper metal and KI may be usedduring this step C, in this case Z represents 1.

Likewise, HBF₄ as a mixture with NaNO₂ may be used. Z then represents F.

During step D, the compounds of formula (II) give the compound offormula (I). An alcohol of formula R²OH, in which R² represents a groupsuch as those defined above, preferably a C₁-C₁₀ alkyl, still morepreferably an n-butyl group, is used. The choice of the base used toform the alcoholate is within the capability of persons skilled in theart who may in particular use an alkali or alkaline-earth metalhydroxide or hydride, an alkali metal or an alkaline-earth metal,preferably KOH, NaH or sodium metal.

Another aspect of the present invention relates to a further improvedmethod for preparing this same compound of formula (I) obtained directlyby diazotization and decomposition of a compound of formula (III) bymeans of a compound AZ_(n) which is preferably a metal alkoxide. In thiscase, steps C and D of the method of the invention are replaced by asingle step C′.

The various substituents of the compounds then have the same meanings asabove.

Another variant of the method of the invention consists in replacingstep D with step D′. In this case, a compound of formula (II) in which Zrepresents a group —OR³ is used, it is then possible to displace thisgroup by a more appropriate similar group. For example, in the casewhere Z is an ethoxy group, it will be possible to displace it by abutoxy group which may be introduced by treating with sodium butoxide.The use of such a substitution constitutes an additional method of thepresent invention for the preparation of a compound of formula (I)starting from a compound of formula (II).

The methods of the invention which are particularly preferred allow thepreparation of compounds of formula (I) by means of the compounds offormulae (II) to (V) in which the following characteristics are presentalone or in combination:

-   -   the iodine atom is in the 6-position of the chromone;    -   R¹ represents a C₁-C₁₀ alkyl, preferably an n-propyl;    -   R² represents a C₁-C₁₀ alkyl, preferably an n-butyl;    -   R⁴ represents a C₁-C₁₀ alkyl, preferably a methyl;    -   A represents Cu;    -   Z represents a halogen atom, preferably Cl or Br, more        preferably Cl, or the group —OR³ in which R³ represents a methyl        or n-butyl group.

Most preferably, the methods of the invention are used for thepreparation of a compound of formula (I) in which R¹ represents ann-propyl and R² represents an n-butyl.

As compounds which are advantageously prepared by means of the methodsof the invention, there may be mentioned in particular

-   2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one-   2-ethoxy-6-ioxo-3-propyl-4H-1-benzopyran-4-one-   6-iodo-2-propoxy-3-propyl-4H-1-benzopyran-4-one-   2-but-2-ynyloxy-6-iodo-3-propyl-4H-1-benzopyran-4-one-   6-iodo-2-(1-methylbutoxy)-3-propyl-4H-1-benzopyran-4-one-   2-but-3-enyloxy-6-iodo-3-propyl-4H-1-benzopyran-4-one-   3-butyl-6-iodo-2-isopropoxy-4H-1-benzopyran-4-one-   6-iodo-3-propyl-2-(tetrahydropyran-4-yloxy)-4H-1-benzopyran-4-one-   6-iodo-3-propyl-2-(2,2,2-trifluoroethoxy)₄H-1-benzopyran-4-one

Moreover, persons skilled in the art will know how to adapt the methodsof the invention to the preparation of the compounds of formula (I) to(V) in the form of their possible geometric and/or optical isomers, pureor as mixtures, in all proportions, including the possible racemicmixture(s), their optional N-oxides, addition salts with an acid, whichare acceptable for use in the crop protection field, and their possiblemetal and/or metalloid complexes, which are acceptable for use in thecrop protection field.

The methods of the invention have been described in relation toiodinated chromone derivatives. However, these methods may be adaptedfor the preparation of other halogenated chromone derivatives.

An additional aspect of the present invention relates to intermediatecompounds useful for the methods of preparation according to theinvention.

These compounds are the compounds of formula (III) and the compounds offormula (II) in which the various substituents have the same meaning asabove.

Excluded however are the compounds of formula (II) for which the iodineatom is in the 6-position, R¹ represents an n-propyl group and R³represents a methyl group or an n-propyl group.

Among the intermediate compounds of formula (III), there are preferredthose in which the following characteristics are present alone or incombination:

-   -   the iodine atom is in the 6-position of the chromone;    -   R¹ represents a C₁-C₁₀ allyl group, preferably an n-propyl        group.

Among the intermediate compounds of formula (II), there are preferredthose in which the following characteristics are present alone or incombination:

-   -   the iodine atom is in the 6-position of the chromone;    -   R¹ represents a C₁-C₁₀ alkyl group;    -   Z represents a halogen atom.

More preferably, R¹ represents an n-propyl group and Z representschlorine or bromine.

The following examples are given without limitation in order to furtherillustrate the present invention.

EXAMPLE 1 Preparation of 2-amino-6-iodo-3-propylchromone

A solution of 8.4 ml (0.06 mol) of diisopropylamine in 20 ml ofanhydrous THF, cooled to −20° C., is treated by adding 30 ml (0.06 mol)of 2 M n-butyllithium in solution in hexanes over 15 minutes. Thesolution is kept stirring at this temperature for 5 minutes and 2.10 ml(0.02 mol) of valeronitrile are added at −20° C. over 5 minutes. Thesolution is kept stirring at −20° C. for 15 minutes and a solution of5.84 g (0.02 mol) of ethyl 4-iodosalicylate in 20 ml of anhydrous THF isadded over 15 minutes. The suspension is heated to 5° C. and keptstirring for 45 minutes and then hydrolyzed with 15 ml of a saturatedaqueous NH₄Cl solution. The biphasic solution is kept stirring for 2hours. The aqueous phase is then removed, the organic phase is washedwith 2×20 ml of water and then 20 ml of a saturated aqueous NaClsolution. The organic phase is dried over MgSO₄, filtered andconcentrated to dryness, which gives 7.25 g of a yellow solid (70%). Theproduct crystallized from acetonitrile has a melting point of 186-188°C.

EXAMPLE 2 Preparation of 2-chloro-6-iodo-3-propylchromone

To a suspension of 1.98 g (6 mmol) of 2-amino-6-iodo-3-propylchromone,1.22 g (7.2 mmol) of CuCl₂.2H₂O in 60 ml of acetonitrile, cooled to 0°C. is added 0.86 ml (7.2 mmol) of tert-butylnitrite over 10 minutes. Thereaction mixture is heated to 20° C. and kept stirring at thistemperature for 3 hours. The solution is hydrolyzed by adding 60 ml ofwater and extracted with 2×50 ml of ethyl acetate. The organic phasesare combined and washed with 20 ml of NH₄OH, 2×50 ml of water and then50 ml of a saturated aqueous NaCl solution. The organic phase is driedover MgSO₄, filtered and concentrated to dryness. This gives 2.04 g of abrown solid (78% theoretical yield) having a melting point of 103-105°C.

EXAMPLE 3 Preparation of 2-butoxy-6-iodo-3-propylchromone

To a solution of 1.05 g (3 mmol) of 2-chloro-6-iodo-3-propylchromone in10 ml of dichloromethane are added, at 20° C., 2.4 ml (4.3 mmol) of a20% solution of sodium n-butoxide in n-butanol. The solution is kept at20° C. for 2 hours and then heated at 40° C. for 4 hours. The reactionmedium is hydrolyzed with 10 ml of water and the organic phase is washedwith 2×10 ml of water, dried over MgSO₄, filtered and concentrated todryness. This gives 0.95 g of a brown oil which crystallizes. Theproduct crystallized from acetonitrile has a melting point of 69-71° C.

EXAMPLE 4 Preparation of 6-iodo-2-methoxy-3-propylchromone

To a suspension of 0.31 g (0.95 mmol) of2-amino-6-iodo-3-propylchromone, 0.15 g (1.2 mmol) of Cu(OMe)₂ in 2 mlof acetonitrile is added, at 20° C., 0.14 ml (1.2 mmol) oftert-butylnitrite over 5 minutes. The reaction medium is heated to 60°C. and kept stirring at this temperature for 3 hours. After returning toroom temperature, the reaction mixture is hydrolyzed by adding 1 ml ofwater and extracted with 2×5 ml of ethyl acetate. The organic phases arecombined and washed with 5 ml of NH₄OH, 2×5 ml of water and then 5 ml ofa saturated aqueous NaCl solution. The organic phase is dried overMgSO₄, filtered and concentrated to dryness.

EXAMPLE 5 Preparation of 2-n-butoxy-6-iodo-3-propylchromone

To a solution of 0.27 g (0.76 mol) of 2-ethoxy-6-iodo-3-propylchromonein 2.5 ml of n-butanol is added, at 20° C., 0.5 ml (0.91 mmol) of a 20%(w/w) solution of sodium n-butoxide in n-butanol over 5 minutes. Thereaction medium is kept stirring at 20° C. for 2 hours. The reactionmixture is treated by adding 2 ml of an aqueous 0.1 N HCl solution andextracted with 10 ml of dichloromethane. The organic phase is extractedand washed with 2×5 ml of water. The organic phase is dried over MgSO₄,filtered and concentrated to dryness. This gives 0.24 g of a brown oilwhich crystallizes.

1. A method for preparing a compound of formula (I)

according to the following steps: step A: reaction of a compound offormula (V)

with a nitrile of formula R¹CH₂CN and a base to form the compound offormula (IV);

step B: compound of formula (IV) which is then cyclized in an aqueousacid medium to form the compound of formula (III):

step C: compound of formula (III) which gives the compound of formula(II) via a diazotization reaction by means of a compound chosen fromsodium nitrite in the form of a mixture with an acid, alkyl nitrites,alkyl thionitrites and alkyl thionitrates, and decomposition by means ofa compound AZ_(n);

step D: compound of formula (II) which gives the compound of formula (I)by the action of an alcohol in the form of a mixture with a base; in theformulae (I) to (V) R¹, R², R³ and R⁴, which are identical or different,represent a C₁-C₁₀ alkyl, C₁-C₁₀ alkenyl or C₁-C₁₀ alkynyl, one or morecarbo- or heterocycles having 5 to 7 atoms, it being possible for thesegroups to be substituted or unsubstituted; A represents a metal or ametal salt; Z represents a group chosen from Cl, Br or —OR³; n is equalto 0, 1 or
 2. 2. A method according to claim 1, for which the base usedduring step A is lithium diisopropylamide.
 3. A method according toclaim 1, for which the acid used during step B is acetic acid.
 4. Amethod according to claim 1, for which A is copper.
 5. A methodaccording to claim 1, in which step C uses t-butyl or methyl nitrite. 6.A method according to claim 1, for which AZ_(n) represents Cu(OR³)₂ orCuCl₂.
 7. A method according to claim 1, in which step C uses t-butyl ormethyl nitrite and for which AZ_(n) represents Cu(OR³)₂ or CuCl₂.
 8. Amethod according to claim 1, in which step C uses sodium nitrite in theform of a mixture with HCl or H₂SO₄.
 9. A method according to claim 1,for which AZ_(n) represents Cu(OR³) or CuCl.
 10. A method according toclaim 1, in which step C uses sodium nitrite in the form of a mixturewith HCl or H₂SO₄ and for which AZ_(n) represents Cu(OR³) or CuCl.
 11. Amethod according to claim 1, in which step D uses an alcohol of formulaR²OH in which R² is a C₁-C₁₀ alkyl.
 12. A method according to claim 11,for which R² represents n-butyl.
 13. A method according to claim 1, inwhich step D is replaced by step D′ and in which there is used acompound of formula (II) in which Z represents a group —OR³, which isdisplaced by a similar, more appropriate group.
 14. A method accordingto claim 13, for which Z is the ethoxy group which is displaced by abutoxy group introduced by treating with sodium butoxide.
 15. A methodaccording to claim 1, in which step A is replaced by step A′ and inwhich there is used a nitrite of formula R¹CXHCN, in which X representsa halogen atom, with, as base, a metal chosen from magnesium or zinc.16. A method according to claim 1, for which the followingcharacteristics are present alone or in combination: the iodine atom isin the 6-position of the chromone; R¹ represents a C₁-C₁₀ alkyl,preferably an n-propyl; R² represents a C₁-C₁₀ alkyl, preferably ann-butyl; R⁴ represents a C₁-C₁₀ alkyl, preferably a methyl; A representsCu; Z represents Cl or Br, or the group —OR³ in which R³ represents amethyl or n-butyl group.
 17. The method as claimed in claim 1, for whichthe preparation of a compound of formula (I) in which R¹ represents ann-propyl and R² represents an n-butyl.
 18. A method for preparing acompound of formula (III)

according to the following steps: reaction of a compound of formula (V)

with a nitrile of formula R¹CH₂CN and a base to form the compound offormula (IV);

which compound of formula (IV) is then cyclized in an aqueous acidmedium to form the compound of formula (III); in formulae (III) to (V)R¹, R², R³ and R⁴, which are identical or different, represent a C₁-C₁₀alkyl, C₁-C₁₀ alkenyl or C₁-C₁₀ alkynyl, one or more carbo-heterocycleshaving from 5 to 7 atoms, it being possible for these groups to besubstituted or unsubstituted.
 19. A method for preparing a compound offormula (II)

from a compound of formula (III) which gives the compound of formula(II) via a diazotization reaction

by means of a compound chosen from sodium nitrite in the form of amixture with an acid, alkyl nitrites, alkyl thionitrites and alkylthionitrates; and decomposition by means of a compound AZ_(n); in theformulae (II) and (III) R¹ and R³, which are identical or different,represent a C₁-C₁₀ alkyl, C₁-C₁₀ alkenyl or C₁-C₁₀ alkynyl, one or morecarbo- or heterocycles having 5 to 7 atoms, it being possible for thesegroups to be substituted or unsubstituted; A represents a metal or ametal salt; Z represents a group chosen from Cl, Br or —OR³; n is equalto 0, 1 or
 2. 20. A method for preparing a compound of formula (I)

from a compound of formula (II) which gives the compound of formula (I)

by the action of an alcohol in the form of a mixture with a base; in theformulae (I) and (II) R¹ and R², which are identical or different,represent a C₁-C₁₀ alkyl, C₁-C₁₀ alkenyl or C₁-C₁₀ alkynyl, one or morecarbo- or heterocycles having 5 to 7 atoms, it being possible for thesegroups to be substituted or unsubstituted; Z represents a group chosenfrom Cl, Br or —OR³.
 21. A compound of formula (III)

in which R¹ represents a C₁-C₁₀ alkyl, C₁-C₁₀ alkenyl or C₁-C₁₀ alkynyl,one or more carbo- or heterocycles having from 5 to 7 atoms, it beingpossible for these groups to be substituted or unsubstituted.
 22. Thecompound as claimed in claim 21, of formula (III) in which the followingcharacteristics are present alone or in combination: the iodine atom isin the 6-position of the chromone; R¹ represents a C₁-C₁₀ alkyl group.23. The compound as claimed in claim 21, of formula (III) in which R¹represents the n-propyl group.
 24. A compound of formula (II)

in which R¹ and R³, which are identical or different, represent a C₁-C₁₀alkyl, C₁-C₁₀ alkenyl or C₁-C₁₀ alkynyl, one or more carbo- orheterocycles having 5 to 7 atoms, it being possible for these groups tobe substituted or unsubstituted; Z represents a halogen atom.
 25. Acompound according to claim 24, of formula (II) in which the followingcharacteristics are present alone or in combination: the iodine atom isin the 6-position of the chromone; R¹ represents a C₁-C₁₀ alkyl group.26. A compound according to claim 24, of formula (II) in which R¹represents an n-propyl group and Z represents chlorine or bromine.
 27. Acompound according to claim 25, of formula (II) in which R¹ representsan n-propyl group and Z represents chlorine or bromine.